Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy-particularly the checkpoint inhibitors-have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed reports on response rates in hepatitis viral-related HCC as compared with nonviral HCC. Given such complexity in response to immunotherapy, it is increasingly appreciated that deeper understanding of the tumor molecular features and tumor microenvironment of hepatitis viral-related HCC is crucial for the design of more effective immunotherapeutics. We discuss herein the current knowledge in tumor genomic mutational and immune landscapes as well as the ongoing immunotherapy trials in HCC with the unique focus on their viral etiologies. Based on this understanding, we also outline perspectives and rationale on the design of potential immunotherapeutic strategies in HCC patients according to their viral etiologies.